Synergistic microbicidal combinations containing 3-isothiazoline and commercial biocides

ABSTRACT

The invention relates to synergistic antimicrobial and biocidal compositions comprising 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one and one or more commercial biocides for more effective, and broader control of microorganisms in various industrial systems.

CROSS REFERENCE TO RELATED APPLICATION

This is a divisional of Ser. No. 567,201 Aug. 14, 1990, now U.S. Pat.No. 5,132,306, which was in turn a divisional of Ser. No. 444,571 ofDec. 1, 1989, which was in turn a divisional of Ser. No. 289,066 of Dec.22, 1988, now U.S. Pat. No. 4,906,651.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to synergistic biocidal combinations including anisothiazolone and one or more of many commercial biocides for moreeffective and broader control of micro-organisms in various industrialsystems. In particular, the present invention relates to the use of amixture of 5-chloro-2-methyl-4-isothiazolin-3-one and2-methyl-4-isothiazolin-3-one (also known as5-chloro-2-methyl-3-isothiazolone and 2-methyl-3-isothiazolone,respectively) with one or more of the following 14 compounds:Hexahydro-1,3,5-triethyl-5-triazine; 5-bromo-5-nitro-1,3-dioxane;2-(hydroxymethyl)aminoethanol 2-(hydroxymethyl)amino-2-methylpropanol;α-benzoyl-α-chloroformaldoxime; benzylbromoacetate; p-chloro-m-xylenol;bis-(2-hydroxy-5-chlorophenyl)sulfide; p-tolydiiodmethylsulfone;3-iodo-2-propynylbutylcarbamate;bis-(2-hydroxy-5-chlorophenyl)methylene; dipropylamine ether;dodecylamine; and 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantanechloride.

2. Prior Art

The isothiazolones are described in U.S. Pat. Nos. 3,761,488; 4,105,431;4,252,694; 4,265,899 and 4,279,762. An excellent antimicrobial agent isa mixture of 75% 5-chloro-2-methyl-4-isothiazolin-3-one and 25%2-methyl-4-isothiazolin-3-one which is very effective against bacteria,fungi, and algae. The suggested dosages, sometimes, cannot achieve thebest results for the control of microorganisms due to interferingnucleophiles, or due to less sensitive organisms in certain systems. Tocontrol the situations like these will need higher concentration ofactive ingredient which becomes more costly in the treatment. Therefore,the search for more effective and broader control method to achieve thebest results has continued.

Many other broad classes of biocidal agents are known. They arecommercially available for the control of microorganisms in certainsections of various industrial systems such as paints, wood, textile,paper, pulp, leather, fur, tobacco, rope, plastics, fuel, oil,cosmetics, rubber, adhesives, latex emulsions, joint cements, watertreatment, laundry, and metalworking industries, and the like. Ingeneral, high dosage requirements make them disadvantageous because ofhigh treatment cost and interference with the formulation of finishedproduct or the operation of the system. Sometimes many biocides cannotprovide satisfactory performances even at high use concentrations due toweak activity against certain bacteria or fungi. Without effectivecontrol, loss of product, inferior product, production-time loss, healthhazard, and other types of problems may occur in the systems.

It has been discovered that combinations of a mixture of5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-onewith one or more of the 14 compounds within a specified range of ratiosresults in synergistic biocidal activities against a wide range ofmicroorganisms. The synergy in which the disruptive interaction on theorganisms by the two compounds together is greater than the sum of bothcompounds taken alone does not arise from the expected activity of thecomponents or from the expected improvement in activity. The synergisticcombinations provide more effective and broader control ofmicroorganisms in a number of industrial systems.

It is the principal object of this invention to provide the use ofsynergistic compositions which overcome the disadvantages of the priorart biocidal compositions.

Important applications of the synergistic antimicrobial compositions ofthe present invention include but are not limited to: inhibiting thegrowth of bacteria and fungi in aqueous and organic paints, adhesives,latex emulsions, and joint cements; preserving wood; preserving cuttingfluids, controlling slimeproducing bacteria and fungi in pulp andpapermills and cooling towers; as a spray or dip treatment for textilesand leather to prevent mold growth; protecting paint films, especiallyexterior paints from attack by fungi which occurs during weathering ofthe paint film; protecting processing equipment from slime depositsduring manufacture of cane and beet sugar; preventing microorganismbuildup and deposits in air washer or scrubber systems and in industrialfresh water supply systems; controlling micro-organisms contaminationand deposits in oil field drilling fluids and muds, and in secondarypetroleum recovery processes; preventing bacterial and fungal growth inpaper coating processes; controlling bacterial and fungal growth anddeposits during the manufacture of various speciality boards, e.g.,cardboard and particle board; preventing sap stain discoloration onfreshly cut wood of various kinds; controlling bacterial fungal growthin clay and pigment slurries of various types; as a hard surfacedisinfectant to prevent growth of bacteria and fungi on walls, floors,etc.; in swimming pools to prevent algae growth; inhibiting the growthof harmful bacteria, yeasts, fungi on plants, trees, fruits, seeds, orsoil; protecting animal dip compositions against the buildup ofmicroorganisms, and in photoprocessing to prevent buildup ofmicroorganisms, and the like.

The synergistic compositions of this invention may be added separatelyto an industrial system or may be formulated as a simple mixturecomprising its essential ingredients, or together with a suitablecarrier or solvent, or as an aqueous emulsion or dispersion.

SUMMARY OF THE INVENTION

Microbiocidal compositions comprising a synergistic mixture the firstcomponent being a 3:1 ratio of 5-chloro-2-methyl-4-isothiazolin-3-oneand 2-methyl-4-isothiazolin-3-one (Compound A) and the second componentwhich is one or more of the following compounds (Compound B) wherein therange of ratios of Compound A to Compound B (A:B) is from 8:1 to 1:200exhibit synergistic biocidal and antimicrobial activity against a widerange of microorganisms. More particularly, the invention relates to theuse of a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and2-methyl-4-isothiazolin-3-one in combination with one or more of thefollowing 14 compounds: Hexahydro-1,3,5-triethyl-5-triazine;5-bromo-5-nitro-1,3-dioxane; 2-(hydroxymethyl)amino-ethanol;2-(hydroxymethyl)amino-2-methylpropanol; α-benzoyl-α-chloroformaldoxime;benzylbromoacetate; p-chloro-m-xylenol;bis-(2-hydroxy-5-chlorophenyl)sulfide; p-tolyldiiodomethylsulfone;3-iodo-2-propynylbutylcarbamate;bis-(2-hydroxy-5-chlorophenyl)methylene; dipropylamine ether;dodecylamine; and 1-(3-chloroally)-3,5,7-triaza-1-azoniaadamantanechloride.

The invention also relates to a method of inhibiting the growth ofbacteria, fungi or algae in a locus subject to contamination bybacteria, fungi or algae, which comprises incorporating into or onto thelocus in an amount which is effective to adversely affect the growth ofbacteria, fungi or algae one or more of the synergistic combinationsdescribed above.

The composition of the invention can be formulated as a solutions inwater. While the amount of the instant composition in the formulatedsolution can vary over a wide range, the solutions can conveniently beformulated to contain from about 5 to about 100 ppm of the compositionin solution, with the preferred range being from about 10 to 50 ppm ofthe composition. In formulating the solutions, other solvents which arewater-miscible, such as ethyl alcohol, propyl alcohol, isopropylalcohol, diethylene glycol, dipropylene glycol, polyethylene glycol,diethylene glycol ethyl ether, and the like, may be employed in order toaid in solubilizing the active components. Furthermore, various otherconventional additives may be employed, such as surfactants, dispersingagents, corrosion inhibitors, and the like.

In general, the ratio of the first component to second component is inthe range of from about 8:1 to 1:200. The other ratios are given in theexamples.

GENERAL DESCRIPTION OF THE PREFERRED EMBODIMENT

The synergistic combinations have a wide range of applications,including all areas where the individual biocides and preservatives arecurrently employed. In addition, the synergistic combinations can beused beyond their original intended uses because of the newly-acquired,more effective broader spectrum of activities.

The synergism of these two-component combinations is demonstrated bytesting a wide range of concentrations and ratios of compounds,generated two-fold serial dilutions in a liquid growth medium of abiocide in one dimension and another biocide in the second dimension,against a bacterium Escherichia coil (ATCC 11229) or a fungus Candidaalbicans (ATCC 11651), or a mixed culture of bacteria and fungi whichare natural contaminants of a metalworking fluid, or a more tolerantpseudomonad isolated from a surfactant. Each test tube was inoculated toabout 2×10⁷ bacteria per ml or 2×10⁶ fungi per ml. The lowestconcentrations of each compound or mixtures to inhibit visible growth(turbidity) at 37° for E. coli and at 30° C. for the pseudomonad, C.albicans, or the mixed culture for over 2 days is the minimum inhibitoryconcentration (MIC). The lowest concentration of each compound or themixtures to kill 99.99% of fungi or 99.999% of bacteria after certainperiods of exposure from 1 day to 7 days is taken as minimum biocidalconcentration (MBC). Both MIC and MBC are taken as end points ofactivity. End points for the mixtures of compound A and compound B werethen compared with the end points for compound A alone and compound Balone. Synergism was determined by an industrially accepted methoddescribed by Kull, F. C.; Eisman, P. C.; Sylwestrowicz, H. D. and Mayer,R. L., in applied Microbiology 9:538-541 (1961) using the ratiodetermined by ##EQU1## wherein QA=concentration of compound A in partsper million (ppm), acting alone, which produced an end point.

Qa=concentration of compound A in ppm, in the mixture, which produced anend point.

QB=concentration of compound B in ppm, acting lone, which produced anend point.

Qb=concentration of compound B in ppm, in the mixture, which produced anend point

when the sum of Qa/QA and Qb/QB is greater than one, antagonism isindicated. When the sum is equal to one additivity is indicated, andwhen less than one synergism is demonstrated.

The test results for demonstration of synergism of biocide combinationsare shown in Table 1 through Table 14. Each table is organized to show:

1. the specific combination of compound A and compound B;

2. test against E. coli (Ecol), or C. albicans (Calb), or a pseudomonadspecies (P. sp), or a mixed culture of bacteria and fungi (mixed);

3. test medium by either trypticase soy broth (TSB) or a minimal saltmedium +0.2% glucose (M9G);

4. the method of evaluation (test) by either MIC or MBC. The MBC1d meansMBC determined after 1-day exposure to biocides. MBC2d means MBCdetermined after 2-days exposure to biocides, etc.;

5. the end-point activity in ppm measured by MIC or MBC for compound Aalone (QA), for compound B alone (QB), for compound A in the mixture(Qa), or for compound B in the mixture (Qb);

6. the calculation for synergy index (SI) based on the formulaSI=Qa/QA+Qb/QB, and for the ratio of compound A to compound B in thesynergistic combinations (Qa:Qb);

7. the range of ratios for synergism and the preferred ratios.

                                      TABLE 1                                     __________________________________________________________________________    Combination of 5-chloro-2-methyl-4-isothiazolin-3-one and                     2-methyl-4-isothiazolin-3-one (Compound A) and hexahydro-                     1,3,5-triethyl-s-triazine (Compound B)                                                      end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  2.5                                                                              250.0                                                                             1.3                                                                              62.0                                                                              0.50                                                                              0.25                                                                              0.75                                               MBC2d                                                                              5.0                                                                              1000.0                                                                            0.6                                                                              250.0                                                                             0.12                                                                              0.25                                                                              0.37                                                    5.0                                                                              1000.0                                                                            2.5                                                                              8.0 0.50                                                                              0.01                                                                              0.51                                               MBC6d                                                                              5.0                                                                              500.0                                                                             0.6                                                                              250.0                                                                             0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              500.0                                                                             1.3                                                                              125.0                                                                             0.25                                                                              0.25                                                                              0.50                                                    5.0                                                                              500.0                                                                             2.5                                                                              4.0 0.50                                                                              0.01                                                                              0.51                                      Calb TSB MlC  1.3                                                                              1000.0                                                                            0.3                                                                              500.0                                                                             0.25                                                                              0.50                                                                              0.75                                                    1.3                                                                              1000.0                                                                            0.6                                                                              250.0                                                                             0.50                                                                              0.25                                                                              0.75                                               MBC2d                                                                              1.3                                                                              1000.0                                                                            0.3                                                                              500.0                                                                             0.25                                                                              0.50                                                                              0.75                                                    1.3                                                                              1000.0                                                                            0.6                                                                              250.0                                                                             0.50                                                                              0.25                                                                              0.75                                               MBC6d                                                                              1.3                                                                              1000.0                                                                            0.3                                                                              500.0                                                                             0.25                                                                              0.50                                                                              0.75                                                    1.3                                                                              1000.0                                                                            0.6                                                                              250.0                                                                             0.50                                                                              0.25                                                                              0.75                                      P.sp TSB MlC  8.0                                                                              250.0                                                                             1.0                                                                              125.0                                                                             0.13                                                                              0.50                                                                              0.63                                                    8.0                                                                              250.0                                                                             2.0                                                                              62.0                                                                              0.25                                                                              0.25                                                                              0.50                                                    8.0                                                                              250.0                                                                             4.0                                                                              31.0                                                                              0.50                                                                              0.12                                                                              0.62                                               MBC2d                                                                              31.0                                                                             500.0                                                                             4.0                                                                              125.0                                                                             0.13                                                                              0.25                                                                              0.38                                                    31.0                                                                             500.0                                                                             8.0                                                                              62.0                                                                              0.26                                                                              0.12                                                                              0.38                                                    31.0                                                                             500.0                                                                             16.0                                                                             4.0 0.52                                                                              0.01                                                                              0.52                                               MBC6d                                                                              31.0                                                                             500.0                                                                             4.0                                                                              125.0                                                                             0.13                                                                              0.25                                                                              0.38                                                    31.0                                                                             500.0                                                                             8.0                                                                              62.0                                                                              0.26                                                                              0.12                                                                              0.38                                                    31.0                                                                             500.0                                                                             16.0                                                                             4.0 0.52                                                                              0.01                                                                              0.52                                      Ecol M9G MlC  0.6                                                                               31.0                                                                             0.3                                                                              2.0 0.50                                                                              0.06                                                                              0.56                                               MBCld                                                                              0.6                                                                               31.0                                                                             0.3                                                                              2.0 0.50                                                                              0.06                                                                              0.56                                      Mixed                                                                              TSB MlC  3.1                                                                              250.0                                                                             0.6                                                                              62.0                                                                              0.20                                                                              0.25                                                                              0.45                                               MBCld                                                                              25.0                                                                             1000.0                                                                            2.5                                                                              250.0                                                                             0.10                                                                              0.25                                                                              0.35                                               MBC4d                                                                              3.1                                                                              250.0                                                                             0.6                                                                              62.0                                                                              0.20                                                                              0.25                                                                              0.45                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 4:1 to 1:1600.     The preferred ratios are 4:1 to 1:100.                                   

                                      TABLE 2                                     __________________________________________________________________________    Combination of Compound A and 5-Bromo-5-nitro-1,3-dioxane (Compound B)                      end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  2.5                                                                              25.0                                                                              0.6                                                                              12.5                                                                              0.25                                                                              0.50                                                                              0.75                                                    2.5                                                                              25.0                                                                              1.3                                                                              3.1 0.50                                                                              0.12                                                                              0.62                                               MBC2d                                                                              5.0                                                                              25.0                                                                              1.3                                                                              12.5                                                                              0.25                                                                              0.50                                                                              0.75                                               MBC6d                                                                              5.0                                                                              25.0                                                                              1.3                                                                              6.2 0.25                                                                              0.25                                                                              0.50                                                    5.0                                                                              25.0                                                                              2.5                                                                              0.8 0.50                                                                              0.03                                                                              0.53                                      Calb TSB MlC  1.3                                                                              25.0                                                                              0.3                                                                              12.5                                                                              0.25                                                                              0.50                                                                              0.75                                                    1.3                                                                              25.0                                                                              0.6                                                                              6.2 0.50                                                                              0.25                                                                              0.74                                               MBC2d                                                                              1.3                                                                              50.0                                                                              0.1                                                                              25.0                                                                              0.06                                                                              0.50                                                                              0.56                                                    1.3                                                                              50.0                                                                              0.6                                                                              6.2 0.50                                                                              0.12                                                                              0.62                                               MBC6d                                                                              2.5                                                                              50.0                                                                              0.2                                                                              25.0                                                                              0.06                                                                              0.50                                                                              0.56                                                    2.5                                                                              50.0                                                                              0.6                                                                              6.2 0.25                                                                              0.12                                                                              0.37                                                    2.5                                                                              50.0                                                                              1.3                                                                              0.2 0.50                                                                              0.00                                                                              0.50                                      P.sp TSB MlC  16.0                                                                             50.0                                                                              1.0                                                                              25.0                                                                              0.06                                                                              0.50                                                                              0.56                                                    16.0                                                                             50.0                                                                              8.0                                                                              12.5                                                                              0.50                                                                              0.25                                                                              0.75                                               MBC2d                                                                              31.0                                                                             100.0                                                                             1.0                                                                              50.0                                                                              0.03                                                                              0.50                                                                              0.53                                                    31.0                                                                             100.0                                                                             16.0                                                                             12.5                                                                              0.52                                                                              0.13                                                                              0.64                                               MBC6d                                                                              31.0                                                                             100.0                                                                             1.0                                                                              50.0                                                                              0.03                                                                              0.50                                                                              0.53                                                    31.0                                                                             100.0                                                                             16.0                                                                             25.0                                                                              0.52                                                                              0.25                                                                              0.77                                      Ecol M9G MlC  0.6                                                                              6.2 0.3                                                                              1.6 0.50                                                                              0.26                                                                              0.76                                                    0.6                                                                              6.2 0.2                                                                              3.1 0.26                                                                              0.50                                                                              0.76                                               MBCld                                                                              0.6                                                                              6.2 0.3                                                                              1.6 0.50                                                                              0.26                                                                              0.76                                                    0.6                                                                              6.2 0.2                                                                              3.1 0.26                                                                              0.50                                                                              0.76                                      Mixed                                                                              TSB MlC  3.1                                                                              12.5                                                                              0.3                                                                              1.6 0.10                                                                              0.13                                                                              0.23                                               MBC4d                                                                              3.1                                                                              25.0                                                                              1.3                                                                              6.2 0.40                                                                              0.25                                                                              0.65                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 6.5:1 to 1:250     The preferred ratios are 6.5:1 to 1:125                                  

                                      TABLE 3                                     __________________________________________________________________________    Combination of Compound A and 2-(Hydroxymethyl)aminoethanol (Compound B)                    end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  5.0                                                                              1000.0                                                                            0.6                                                                              500.0                                                                             0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              1000.0                                                                            1.3                                                                              250.0                                                                             0.25                                                                              0.25                                                                              0.50                                                    5.0                                                                              1000.0                                                                            2.5                                                                              16.0                                                                              0.50                                                                              0.02                                                                              0.52                                               MBC2d                                                                              5.0                                                                              1000.0                                                                            1.3                                                                              250.0                                                                             0.25                                                                              0.25                                                                              0.50                                                    5.0                                                                              1000.0                                                                            2.5                                                                              62.0                                                                              0.50                                                                              0.06                                                                              0.56                                               MBC6d                                                                              5.0                                                                              1000.0                                                                            1.3                                                                              500.0                                                                             0.25                                                                              0.50                                                                              0.75                                                    5.0                                                                              1000.0                                                                            2.5                                                                              125.0                                                                             0.50                                                                              0.13                                                                              0.63                                      Calb TSB MlC  2.5                                                                              1000.0                                                                            1.3                                                                              16.0                                                                              0.50                                                                              0.02                                                                              0.52                                               MBC2d                                                                              2.5                                                                              1000.0                                                                            0.6                                                                              125.0                                                                             0.25                                                                              0.13                                                                              0.37                                               MBC6d                                                                              2.5                                                                              1000.0                                                                            1.3                                                                              16.0                                                                              0.50                                                                              0.02                                                                              0.52                                      P.sp TSB MlC  16.0                                                                             1000.0                                                                            1.0                                                                              500.0                                                                             0.06                                                                              0.50                                                                              0.56                                               MBC2d                                                                              31.0                                                                             1000.0                                                                            8.0                                                                              500.0                                                                             0.26                                                                              0.50                                                                              0.76                                               MBC6d                                                                              31.0                                                                             1000.0                                                                            16.0                                                                             500.0                                                                             0.50                                                                              0.50                                                                              1.00                                      Ecol M9G MlC  0.6                                                                               125.0                                                                            0.1                                                                              31.0                                                                              0.13                                                                              0.25                                                                              0.38                                                    0.6                                                                               125.0                                                                            0.1                                                                              62.0                                                                              0.08                                                                              0.50                                                                              0.58                                               MBCld                                                                              0.6                                                                               125.0                                                                            0.1                                                                              31.0                                                                              0.13                                                                              0.25                                                                              0.38                                                    0.6                                                                               125.0                                                                            0.1                                                                              62.0                                                                              0.08                                                                              0.50                                                                              0.58                                      Mixed                                                                              TSB MlC  3.1                                                                              1000.0                                                                            0.3                                                                              62.0                                                                              0.10                                                                              0.06                                                                              0.16                                               MBCld                                                                              25.0                                                                             1000.0                                                                            0.3                                                                              62.0                                                                              0.01                                                                              0.06                                                                              0.07                                               MBC4d                                                                              3.1                                                                              1000.0                                                                            0.3                                                                              62.0                                                                              0.10                                                                              0.06                                                                              0.16                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:62 to 1:1600     The preferred ratios are 1:25 to 1:200.                                  

                                      TABLE 4                                     __________________________________________________________________________    Combination of Compound A and 2-(hydroxymethyl)amino-2-methylpropanol         (Compound B)                                                                                end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Calb TSB MlC  2.5                                                                              1000.0                                                                            1.3                                                                              500.0                                                                             0.50                                                                              0.50                                                                              1.00                                      Ecol M9G MlC  0.6                                                                               31.0                                                                             0.1                                                                              16.0                                                                              0.13                                                                              0.52                                                                              0.65                                               MBCld                                                                              0.6                                                                               250.0                                                                            0.3                                                                              31.0                                                                              0.50                                                                              0.12                                                                              0.62                                                    0.6                                                                               250.0                                                                            0.1                                                                              62.0                                                                              0.13                                                                              0.25                                                                              0.38                                      Mixed                                                                              TSB MlC  3.1                                                                              1000.0                                                                            0.3                                                                              62.0                                                                              0.10                                                                              0.06                                                                              0.16                                               MBCld                                                                              25.0                                                                             1000.0                                                                            2.5                                                                              500.0                                                                             0.10                                                                              0.50                                                                              0.60                                               MBC4d                                                                              3.1                                                                              1000.0                                                                            0.6                                                                              125.0                                                                             0.20                                                                              0.13                                                                              0.33                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:100 to 1:800     The preferred ratios are 1:100 to 1:200.                                 

                                      TABLE 5                                     __________________________________________________________________________    Combination of Compound A and α-Benzoyl-α-chloroformaldoxime      (Compound B)                                                                                end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol M9G MlC  0.2                                                                               250.0                                                                            0.02                                                                              31.0                                                                             0.13                                                                              0.12                                                                              0.25                                                    0.2                                                                               250.0                                                                            0.08                                                                              0.5                                                                              0.50                                                                              0.00                                                                              0.50                                               MBC4d                                                                              0.2                                                                               500.0                                                                            0.02                                                                              62.0                                                                             0.13                                                                              0.12                                                                              0.25                                                    0.2                                                                               500.0                                                                            0.04                                                                              31.0                                                                             0.25                                                                              0.06                                                                              0.31                                                    0.2                                                                               500.0                                                                            0.08                                                                              16.0                                                                             0.50                                                                              0.03                                                                              0.53                                               MBC7d                                                                              0.2                                                                               250.0                                                                            0.02                                                                              31.0                                                                             0.13                                                                              0.12                                                                              0.25                                                    0.2                                                                               250.0                                                                            0.08                                                                              0.5                                                                              0.50                                                                              0.00                                                                              0.50                                      Calb TSB MlC  1.3                                                                              2000.0                                                                            0.62                                                                             1000.0                                                                            0.50                                                                              0.50                                                                              1.00                                               MBC2d                                                                              1.3                                                                              2000.0                                                                            0.62                                                                             500.0                                                                             0.50                                                                              0.25                                                                              0.75                                      P.sp TSB MlC  4.0                                                                              1000.0                                                                            1.00                                                                             500.0                                                                             0.25                                                                              0.50                                                                              0.75                                                    4.0                                                                              1000.0                                                                            2.00                                                                             125.0                                                                             0.50                                                                              0.13                                                                              0.63                                               MBC2d                                                                              16.0                                                                             2000.0                                                                            1.00                                                                             500.0                                                                             0.06                                                                              0.25                                                                              0.31                                                    16.0                                                                             2000.0                                                                            4.00                                                                             125.0                                                                             0.25                                                                              0.06                                                                              0.31                                                    16.0                                                                             2000.0                                                                            8.0                                                                               16.0                                                                             0.50                                                                              0.01                                                                              0.51                                               MBC6d                                                                              16.0                                                                             2000.0                                                                            1.00                                                                             500.0                                                                             0.05                                                                              0.25                                                                              0.31                                                    16.0                                                                             2000.0                                                                            4.00                                                                             125.0                                                                             0.25                                                                              0.06                                                                              0.31                                                    16.0                                                                             2000.0                                                                            8.00                                                                              31.0                                                                             0.50                                                                              0.02                                                                              0.52                                      Ecol TSB MlC  1.3                                                                              2000.0                                                                            0.62                                                                             500.0                                                                             0.50                                                                              0.25                                                                              0.75                                               MBCld                                                                              1.3                                                                              2000.0                                                                            0.62                                                                             500.0                                                                             0.50                                                                              0.25                                                                              0.75                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:2 to 1:3200.     The preferred ratios are 1:4 to 1:31.                                    

                                      TABLE 6                                     __________________________________________________________________________    Combination of Compound A and Benzyl bromoacetate (Compound B)                              end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  0.6                                                                              62.0                                                                              0.3                                                                              16.0                                                                              0.50                                                                              0.26                                                                              0.76                                               MBCld                                                                              0.6                                                                              62.0                                                                              0.3                                                                              16.0                                                                              0.50                                                                              0.26                                                                              0.76                                      Calb TSB MlC  1.3                                                                              16.0                                                                              0.6                                                                              4.0 0.50                                                                              0.25                                                                              0.75                                               MBCld                                                                              1.3                                                                              16.0                                                                              0.3                                                                              8.0 0.25                                                                              0.50                                                                              0.75                                                    1.3                                                                              16.0                                                                              0.6                                                                              4.0 0.50                                                                              0.25                                                                              0.75                                               MBC4d                                                                              1.3                                                                              16.0                                                                              0.3                                                                              8.0 0.25                                                                              0.50                                                                              0.75                                                    1.3                                                                              16.0                                                                              0.6                                                                              4.0 0.50                                                                              0.25                                                                              0.75                                      Ecol M9G MlC  0.3                                                                              62.0                                                                              0.2                                                                              8.0 0.52                                                                              0.13                                                                              0.65                                                    0.3                                                                              62.0                                                                              0.1                                                                              16.0                                                                              0.16                                                                              0.26                                                                              0.42                                               MBCld                                                                              0.3                                                                              62.0                                                                              0.2                                                                              8.0 0.52                                                                              0.13                                                                              0.65                                                    0.3                                                                              62.0                                                                              0.1                                                                              16.0                                                                              0.16                                                                              0.26                                                                              0.42                                      Mixed                                                                              TSB MlC  3.1                                                                              100.0                                                                             0.6                                                                              8.0 0.20                                                                              0.08                                                                              0.28                                               MBC4d                                                                              3.1                                                                              100.0                                                                             1.3                                                                              16.0                                                                              0.40                                                                              0.16                                                                              0.56                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:6.2 to 1:400     The preferred ratios are 1:6.2 to 1:50.                                  

                                      TABLE 7                                     __________________________________________________________________________    Combination of Compound A and  -p-Chloro- .sub.-- m-xylenol (Compound B)                    end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol M9G MlC  0.3                                                                              250.0                                                                             0.16                                                                             0.3 0.52                                                                              0.00                                                                              0.52                                                    0.3                                                                              250.0                                                                             0.02                                                                             125.0                                                                             0.06                                                                              0.50                                                                              0.56                                               MBCld                                                                              2.5                                                                              250.0                                                                             0.02                                                                             125.0                                                                             0.01                                                                              0.50                                                                              0.51                                                    2.5                                                                              250.0                                                                             0.31                                                                             62.0                                                                              0.12                                                                              0.25                                                                              0.37                                                    2.5                                                                              250.0                                                                             0.62                                                                             31.0                                                                              0.25                                                                              0.12                                                                              0.37                                               MBC4d                                                                              0.3                                                                              250.0                                                                             0.08                                                                             125.0                                                                             0.28                                                                              0.50                                                                              0.78                                                    0.3                                                                              250.0                                                                             0.16                                                                             0.3 0.52                                                                              0.00                                                                              0.52                                               MBC7d                                                                              0.3                                                                              250.0                                                                             0.02                                                                             125.0                                                                             0.06                                                                              0.50                                                                              0.56                                                    0.3                                                                              250.0                                                                             0.16                                                                             0.3 0.52                                                                              0.00                                                                              0.52                                      Calb TSB MlC  2.5                                                                              250.0                                                                             1.25                                                                             31.0                                                                              0.50                                                                              0.12                                                                              0.62                                      Ecol TSB MlC  0.6                                                                              125.0                                                                             0.16                                                                             62.0                                                                              0.26                                                                              0.50                                                                              0.75                                               MBCld                                                                              0.6                                                                              125.0                                                                             0.16                                                                             62.0                                                                              0.26                                                                              0.50                                                                              0.75                                      Mixed                                                                              TSB MlC  3.1                                                                              125.0                                                                             0.31                                                                             62.0                                                                              0.10                                                                              0.50                                                                              0.60                                               MBCld                                                                              25.0                                                                             250.0                                                                             0.62                                                                             125.0                                                                             0.02                                                                              0.50                                                                              0.52                                               MBC4d                                                                              3.1                                                                              125.0                                                                             0.31                                                                             62.0                                                                              0.10                                                                              0.50                                                                              0.60                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:1.6 to           1:6250.                                                                       The preferred ratios are 1:1.6 to 1:200.                                 

                                      TABLE 8                                     __________________________________________________________________________    Combination of Compound A and Bis-(2-hydroxy-5-chlorophenyl)sulfide           (Compound A)                                                                                end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol M9G MlC  0.6                                                                              31.0                                                                              0.2                                                                              8.0 0.26                                                                              0.26                                                                              0.52                                                    0.6                                                                              31.0                                                                              0.1                                                                              16.0                                                                              0.13                                                                              0.52                                                                              0.65                                               MBCld                                                                              0.6                                                                              31.0                                                                              0.2                                                                              8.0 0.26                                                                              0.26                                                                              0.52                                                    0.6                                                                              31.0                                                                              0.1                                                                              16.0                                                                              0.13                                                                              0.52                                                                              0.65                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:50 TO 1:200.     The preferred ratios are 1:50 TO 1:200.                                  

                                      TABLE 9                                     __________________________________________________________________________    Combination of Compound A and  -p-Tolyldiiodomethylsulfone (Compound B)                     end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  5.0                                                                              62.0                                                                              0.6                                                                              31.0                                                                              0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              62.0                                                                              1.3                                                                              8.0 0.25                                                                              0.13                                                                              0.38                                                    5.0                                                                              62.0                                                                              2.5                                                                              0.1 0.50                                                                              0.00                                                                              0.50                                               MBC2d                                                                              5.0                                                                              62.0                                                                              0.6                                                                              31.0                                                                              0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              62.0                                                                              1.3                                                                              8.0 0.25                                                                              0.13                                                                              0.38                                               MBC6d                                                                              5.0                                                                              62.0                                                                              0.6                                                                              31.0                                                                              0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              62.0                                                                              1.3                                                                              8.0 0.25                                                                              0.13                                                                              0.38                                                    5.0                                                                              62.0                                                                              2.5                                                                              4.0 0.50                                                                              0.06                                                                              0.56                                      Calb TSB MlC  1.3                                                                              2.0 0.1                                                                              1.0 0.06                                                                              0.50                                                                              0.56                                                    1.3                                                                              2.0 0.6                                                                              0.5 0.50                                                                              0.25                                                                              0.75                                               MBC2d                                                                              1.3                                                                              2.0 0.2                                                                              1.0 0.13                                                                              0.50                                                                              0.63                                                    1.3                                                                              2.0 0.6                                                                              0.5 0.50                                                                              0.25                                                                              0.75                                               MBC6d                                                                              2.5                                                                              4.0 0.2                                                                              2.0 0.06                                                                              0.50                                                                              0.56                                                    2.5                                                                              4.0 0.6                                                                              1.0 0.25                                                                              0.25                                                                              0.50                                                    2.5                                                                              4.0 1.3                                                                              0.1 0.50                                                                              0.03                                                                              0.53                                      P.sp TSB MlC  8.0                                                                              16.0                                                                              2.0                                                                              8.0 0.25                                                                              0.50                                                                              0.75                                                    8.0                                                                              16.0                                                                              4.0                                                                              4.0 0.50                                                                              0.25                                                                              0.75                                               MBC2d                                                                              31.0                                                                             16.0                                                                              8.0                                                                              8.0 0.26                                                                              0.50                                                                              0.76                                                    31.0                                                                             16.0                                                                              16.0                                                                             2.0 0.52                                                                              0.13                                                                              0.64                                               MBC6d                                                                              31.0                                                                             16.0                                                                              8.0                                                                              8.0 0.26                                                                              0.50                                                                              0.76                                                    31.0                                                                             16.0                                                                              16.0                                                                             2.0 0.52                                                                              0.13                                                                              0.64                                      Ecol M9G MBC2d                                                                              2.5                                                                              25.0                                                                              1.3                                                                              3.1 0.50                                                                              0.12                                                                              0.62                                                    2.5                                                                              25.0                                                                              0.6                                                                              6.2 0.25                                                                              0.25                                                                              0.50                                                    2.5                                                                              25.0                                                                              0.2                                                                              12.5                                                                              0.06                                                                              0.50                                                                              0.56                                      Mixed                                                                              TSB MlC  3.1                                                                              50.0                                                                              0.3                                                                              6.2 0.10                                                                              0.12                                                                              0.22                                               MBC4d                                                                              3.1                                                                              100.0                                                                             0.6                                                                              12.5                                                                              0.20                                                                              0.13                                                                              0.33                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 20:1 to 1:50.      The preferred ratios are 8:1 to 1:20.                                    

                                      TABLE 10                                    __________________________________________________________________________    Combination of Compound A and 3-lodo-2-propynylbutylcarbamate (Compound       B)                                                                                          end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  5.0                                                                              250.0                                                                             0.6                                                                              125.0                                                                             0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              250.0                                                                             1.3                                                                              31.0                                                                              0.25                                                                              0.12                                                                              0.37                                                    5.0                                                                              250.0                                                                             2.5                                                                              0.5 0.50                                                                              0.00                                                                              0.50                                               MBC2d                                                                              5.0                                                                              250.0                                                                             0.6                                                                              125.0                                                                             0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              250.0                                                                             1.3                                                                              31.0                                                                              0.25                                                                              0.12                                                                              0.37                                                    5.0                                                                              250.0                                                                             2.5                                                                              16.0                                                                              0.50                                                                              0.06                                                                              0.56                                               MBC6d                                                                              5.0                                                                              250.0                                                                             0.6                                                                              125.0                                                                             0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              250.0                                                                             1.3                                                                              31.0                                                                              0.25                                                                              0.12                                                                              0.37                                                    5.0                                                                              250.0                                                                             2.5                                                                              2.0 0.50                                                                              0.01                                                                              0.51                                      Calb TSB MlC  1.3                                                                              8.0 0.3                                                                              2.0 0.25                                                                              0.25                                                                              0.50                                                    1.3                                                                              8.0 0.6                                                                              1.0 0.50                                                                              0.13                                                                              0.62                                               MBC2d                                                                              1.3                                                                              8.0 0.3                                                                              4.0 0.25                                                                              0.50                                                                              0.75                                                    1.3                                                                              8.0 0.6                                                                              2.0 0.50                                                                              0.25                                                                              0.75                                               MBC6d                                                                              2.5                                                                              8.0 0.3                                                                              4.0 0.12                                                                              0.50                                                                              0.62                                                    2.5                                                                              8.0 0.6                                                                              2.0 0.25                                                                              0.25                                                                              0.50                                                    2.5                                                                              8.0 1.3                                                                              0.3 0.50                                                                              0.03                                                                              0.53                                      P.sp TSB MlC  8.0                                                                              125.0                                                                             2.0                                                                              62.0                                                                              0.25                                                                              0.50                                                                              0.75                                                    8.0                                                                              125.0                                                                             4.0                                                                              31.0                                                                              0.50                                                                              0.25                                                                              0.75                                               MBC2d                                                                              31.0                                                                             250.0                                                                             2.0                                                                              62.0                                                                              0.06                                                                              0.25                                                                              0.31                                                    31.0                                                                             250.0                                                                             4.0                                                                              31.0                                                                              0.13                                                                              0.12                                                                              0.25                                                    31.0                                                                             250.0                                                                             16.0                                                                             16.0                                                                              0.52                                                                              0.05                                                                              0.58                                               MBC6d                                                                              31.0                                                                             250.0                                                                             1.0                                                                              125.0                                                                             0.03                                                                              0.50                                                                              0.53                                                    31.0                                                                             250.0                                                                             4.0                                                                              62.0                                                                              0.13                                                                              0.25                                                                              0.38                                      Ecol M9G MBC2d                                                                              1.3                                                                              25.0                                                                              0.6                                                                              3.1 0.50                                                                              0.12                                                                              0.62                                                    1.3                                                                              25.0                                                                              0.2                                                                              12.5                                                                              0.13                                                                              0.50                                                                              0.63                                      Mixed                                                                              TSB MlC  3.1                                                                              200.0                                                                             0.6                                                                              12.5                                                                              0.20                                                                              0.06                                                                              0.26                                               MBCld                                                                              25.0                                                                             400.0                                                                             2.5                                                                              50.0                                                                              0.10                                                                              0.13                                                                              0.23                                               MBC4d                                                                              3.1                                                                              200.0                                                                             0.6                                                                              12.5                                                                              0.20                                                                              0.06                                                                              0.26                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 5:1 to 1:200.      The preferred ratios are 1:1 to 1:25.                                    

                                      TABLE 11                                    __________________________________________________________________________    Combination of Compound A and Bis-(2-hydroxy-5-chlorophenyl)-methylene        (Compound B)                                                                                end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  2.5                                                                              62.0                                                                              0.6                                                                              31.0                                                                              0.25                                                                              0.50                                                                              0.75                                                    2.5                                                                              62.0                                                                              1.3                                                                              16.0                                                                              0.50                                                                              0.26                                                                              0.76                                               MBC2d                                                                              5.0                                                                              62.0                                                                              0.6                                                                              31.0                                                                              0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              62.0                                                                              1.3                                                                              16.0                                                                              0.25                                                                              0.26                                                                              0.51                                                    5.0                                                                              62.0                                                                              2.5                                                                              4.0 0.50                                                                              0.06                                                                              0.56                                               MBC6d                                                                              5.0                                                                              62.0                                                                              0.6                                                                              31.0                                                                              0.12                                                                              0.50                                                                              0.62                                                    5.0                                                                              62.0                                                                              1.3                                                                              16.0                                                                              0.25                                                                              0.26                                                                              0.51                                                    5.0                                                                              62.0                                                                              2.5                                                                              2.0 0.50                                                                              0.03                                                                              0.53                                      Calb TSB MlC  2.5                                                                              8.0 1.3                                                                              4.0 0.50                                                                              0.50                                                                              1.00                                               MBC6d                                                                              2.5                                                                              16.0                                                                              1.3                                                                              4.0 0.50                                                                              0.25                                                                              0.75                                      P.sp TSB MlC  16.0                                                                             62.0                                                                              2.0                                                                              31.0                                                                              0.13                                                                              0.50                                                                              0.63                                                    16.0                                                                             62.0                                                                              4.0                                                                              16.0                                                                              0.25                                                                              0.26                                                                              0.51                                                    16.0                                                                             62.0                                                                              8.0                                                                              2.0 0.50                                                                              0.03                                                                              0.53                                               MBC2d                                                                              31.0                                                                             250.0                                                                             2.0                                                                              125.0                                                                             0.06                                                                              0.50                                                                              0.56                                                    31.0                                                                             250.0                                                                             4.0                                                                              16.0                                                                              0.13                                                                              0.06                                                                              0.19                                                    31.0                                                                             250.0                                                                             8.0                                                                              31.0                                                                              0.26                                                                              0.12                                                                              0.38                                                    31.0                                                                             250.0                                                                             16.0                                                                             8.0 0.52                                                                              0.03                                                                              0.55                                               MBC  31.0                                                                             250.0                                                                             1.0                                                                              125.0                                                                             0.03                                                                              0.50                                                                              0.53                                                    31.0                                                                             250.0                                                                             4.0                                                                              62.0                                                                              0.13                                                                              0.25                                                                              0.38                                                    31.0                                                                             250.0                                                                             8.0                                                                              31.0                                                                              0.26                                                                              0.12                                                                              0.38                                                    31.0                                                                             250.0                                                                             16.0                                                                             8.0 0.52                                                                              0.03                                                                              0.55                                      Ecol M9G MlC  0.3                                                                              62.0                                                                              0.1                                                                              31.0                                                                              0.16                                                                              0.50                                                                              0.66                                               MBCld                                                                              0.3                                                                              62.0                                                                              0.1                                                                              31.0                                                                              0.16                                                                              0.50                                                                              0.66                                      Mixed                                                                              TSB MlC  3.1                                                                              125.0                                                                             0.3                                                                              16.0                                                                              0.10                                                                              0.13                                                                              0.23                                               MBCld                                                                              25.0                                                                             125.0                                                                             0.6                                                                              31.0                                                                              0.02                                                                              0.25                                                                              0.27                                               MBC4d                                                                              3.1                                                                              125.0                                                                             0.3                                                                              16.0                                                                              0.10                                                                              0.13                                                                              0.23                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 4:1 to 1:800.      The preferred ratios are 2:1 to 1:50.                                    

                                      TABLE 12                                    __________________________________________________________________________    Combination of Compound A and Dipropylamine ether (Compound B)                              end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol M9G MlC  0.3                                                                              16.0                                                                              0.1                                                                              4.0 0.16                                                                              0.25                                                                              0.41                                                    0.3                                                                              16.0                                                                              0.1                                                                              0.5 0.26                                                                              0.03                                                                              0.29                                               MBCld                                                                              2.5                                                                              62.0                                                                              0.1                                                                              2.0 0.03                                                                              0.03                                                                              0.06                                               MBC4d                                                                              0.3                                                                              31.0                                                                              0.1                                                                              8.0 0.16                                                                              0.26                                                                              0.42                                               MBC7d                                                                              0.3                                                                              31.0                                                                              0.1                                                                              4.0 0.16                                                                              0.13                                                                              0.29                                      Calb TSB MlC  2.5                                                                              62.0                                                                              0.6                                                                              31.0                                                                              0.25                                                                              0.50                                                                              0.75                                                    2.5                                                                              62.0                                                                              1.3                                                                              8.0 0.50                                                                              0.13                                                                              0.63                                      Ecol TSB MlC  1.3                                                                              62.0                                                                              0.1                                                                              16.0                                                                              0.06                                                                              0.26                                                                              0.32                                               MBCld                                                                              1.3                                                                              62.0                                                                              0.3                                                                              31.0                                                                              0.25                                                                              0.50                                                                              0.75                                      Mixed                                                                              TSB MlC  3.1                                                                              200.0                                                                             0.6                                                                              31.0                                                                              0.20                                                                              0.16                                                                              0.36                                               MBC4d                                                                              3.1                                                                              200.0                                                                             1.3                                                                              62.0                                                                              0.40                                                                              0.31                                                                              0.71                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:6.2 to 1:200     The preferred ratios are 1:6.2 to 1:50.                                  

                                      TABLE 13                                    __________________________________________________________________________    Combination of Compound A and Dodecylamine (Compound B)                                     end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Calb TSB MlC  2.5                                                                              25.0                                                                              1.3                                                                              0.4 0.50                                                                              0.02                                                                              0.52                                                    2.5                                                                              25.0                                                                              0.6                                                                              6.2 0.25                                                                              0.25                                                                              0.50                                                    2.5                                                                              25.0                                                                              0.3                                                                              12.5                                                                              0.12                                                                              0.50                                                                              0.62                                               MBC2d                                                                              2.5                                                                              50.0                                                                              1.3                                                                              1.6 0.50                                                                              0.03                                                                              0.53                                                    2.5                                                                              50.0                                                                              0.6                                                                              12.5                                                                              0.25                                                                              0.25                                                                              0.50                                                    2.5                                                                              50.0                                                                              0.3                                                                              25.0                                                                              0.12                                                                              0.50                                                                              0.62                                      Ecol M9G MlC  0.6                                                                              25.0                                                                              0.3                                                                              1.6 0.50                                                                              0.06                                                                              0.56                                                    0.6                                                                              25.0                                                                              0.1                                                                              12.5                                                                              0.13                                                                              0.50                                                                              0.63                                               MBC2d                                                                              1.3                                                                              25.0                                                                              0.6                                                                              1.6 0.50                                                                              0.06                                                                              0.56                                                    1.3                                                                              25.0                                                                              0.3                                                                              3.1 0.25                                                                              0.12                                                                              0.37                                      __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 2.5:1 to 1:160     The preferred ratios are 1:2.5 to 1:20.                                  

                                      TABLE 14                                    __________________________________________________________________________    Combination of Compound A and 1-(3-chloroallyl)-3,5,7-                        triaza-1-azoniaadamantane chloride (Compound B)                                             end point activity in ppm                                                                    calculations                                     Microbe                                                                            Media                                                                             Test QA QB   Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                       __________________________________________________________________________    Ecol M9G MlC  0.3                                                                              31.0 0.04                                                                             8.0 0.13                                                                              0.26                                                                              0.39                                                   0.3                                                                              31.0 0.16                                                                             1.0 0.52                                                                              0.03                                                                              0.55                                              MBC4d                                                                              0.3                                                                              31.0 0.04                                                                             16.0                                                                              0.13                                                                              0.52                                                                              0.65                                                   0.3                                                                              31.0 0.08                                                                             2.0 0.26                                                                              0.06                                                                              0.32                                                   0.3                                                                              31.0 0.16                                                                             1.0 0.52                                                                              0.03                                                                              0.55                                              MBC7d                                                                              0.3                                                                              31.0 0.04                                                                             16.0                                                                              0.13                                                                              0.52                                                                              0.65                                                   0.3                                                                              31.0 0.08                                                                             2.0 0.26                                                                              0.06                                                                              0.32                                                   0.3                                                                              31.0 0.16                                                                             1.0 0.52                                                                              0.03                                                                              0.55                                     Calb TSB MlC  2.5                                                                              500.0                                                                              1.25                                                                             16.0                                                                              0.50                                                                              0.03                                                                              0.53                                     Mixed                                                                              TSB MlC  3.1                                                                              1000.0                                                                             0.62                                                                             125.0                                                                             0.20                                                                              0.13                                                                              0.33                                              MBC4d                                                                              3.1                                                                              1000.0                                                                             0.62                                                                             125.0                                                                             0.20                                                                              0.13                                                                              0.33                                     __________________________________________________________________________     The synergistic ratios of compound A:compound B range from 1:6.2 to 1:400     The preferred ratios are 1:6.2 to 1:200.                                 

                  TABLE 15                                                        ______________________________________                                        Combination of Compound A and 2,4-dichlorobenzyl alcohol                      (Compound B)                                                                            end point      calculations                                         Mic-  Me-           activity in ppm                                                                             Qa/  Qb/                                    robe  dia    Test   QA   QB   Qa   Qb   QA   QB   Sl                          ______________________________________                                        Ecol  TSB    MlC    0.31 500.0                                                                              0.31 500.0                                                                              NA   NA   NA                                                        0.31 250.0                                                                              NA   NA   NA                                                        0.31 125.0                                                                              NA   NA   NA                                                        0.31  62.0                                                                              NA   NA   NA                                                        0.31  31.0                                                                              NA   NA   NA                                                        0.31  0.0 NA   NA   NA                                                        5.0  500.0                                                                              NA   NA   NA                                                        2.5  500.0                                                                              NA   NA   NA                                                        1.25 500.0                                                                              NA   NA   NA                                                        0.62 500.0                                                                              NA   NA   NA                                                        0.16 500.0                                                                              NA   NA   NA                                                        0.08 500.0                                                                              NA   NA   NA                                                        0.00 500.0                                                                              NA   NA   NA                          Ecol  M9G    MlC    0.31 500.0                                                                              0.31 500.0                                                                              NA   NA   NA                                                        0.31 250.0                                                                              NA   NA   NA                                                        0.31 125.0                                                                              NA   NA   NA                                                        0.31  62.0                                                                              NA   NA   NA                                                        0.31  31.0                                                                              NA   NA   NA                                                        0.31  0.0 NA   NA   NA                                                        5.0  500.0                                                                              NA   NA   NA                                                        2.5  500.0                                                                              NA   NA   NA                                                        1.25 500.0                                                                              NA   NA   NA                                                        0.62 500.0                                                                              NA   NA   NA                                                        0.16 500.0                                                                              NA   NA   NA                                                        0.08 500.0                                                                              NA   NA   NA                                                        0.00 500.0                                                                              NA   NA   NA                          ______________________________________                                         NA = not applicable because they are not endpoint activities.            

                                      TABLE 16                                    __________________________________________________________________________    Combination of Compound A and 3,5-dimethyltetrahydro-1,3,5-                   (2H)-thiadiazine-2-thione (Compound B)                                                      end point activity in ppm                                                                   calculations                                      Microbe                                                                            Media                                                                             Test QA QB  Qa Qb  Qa/QA                                                                             Qb/QB                                                                             Sl                                        __________________________________________________________________________    Ecol TSB MlC  0.62                                                                             125.0                                                                             5.0                                                                              31.0                                                                              8.00                                                                              0.25                                                                              8.25                                                    0.62                                                                             125.0                                                                             2.5                                                                              62.0                                                                              4.00                                                                              0.50                                                                              4.50                                               MBCld                                                                              0.62                                                                             125.0                                                                             5.0                                                                              31.0                                                                              8.00                                                                              0.25                                                                              8.25                                                    0.62                                                                             125.0                                                                             2.5                                                                              62.0                                                                              4.00                                                                              0.50                                                                              4.50                                      Ecol M9G MlC  0.16                                                                             62.0                                                                              0.31                                                                             4.0 2.00                                                                              0.06                                                                              2.06                                                    0.16                                                                             62.0                                                                              0.62                                                                             8.0 4.00                                                                              0.12                                                                              4.12                                                    0.16                                                                             62.0                                                                              1.25                                                                             16.0                                                                              8.00                                                                              0.25                                                                              8.25                                               MBCld                                                                              0.16                                                                             62.0                                                                              0.31                                                                             4.0 2.00                                                                              0.06                                                                              2.06                                                    0.16                                                                             62.0                                                                              0.62                                                                             8.0 4.00                                                                              0.12                                                                              4.12                                                    0.16                                                                             62.0                                                                              1.25                                                                             16.0                                                                              8.00                                                                              0.25                                                                              8.25                                      __________________________________________________________________________

As can readily be seen by inspection of Table 1 through Table 14, thecombinations demonstrate synergistic antimicrobial activities asmeasured by minimum inhibitory concentrations (MIC) and synergisticbiocidal activity as measured by minimum biocidal concentrations (MBC),and show surprisingly greater activity than the algebraic sum of theindividual ingredients which make up the respective composition.

The synergistic activities in most cases are applicable to bacteria,fungi, and a mixture of bacteria and fungi. Thus, the combinations notonly lower the use-level of biocide but also broaden the spectrum ofactivity. This is especially useful in situations where Compound A doesnot achieve the best results due to weak activity against certainorganisms. A number of examples, as shown in Tables 1, 2, 3, 5, 9, 10and 11 demonstrate the advantages of using a synergistic combination forthe control of a less sensitive pseudomonad.

Two examples of non-synergistic combinations of Compound A with2,4-dichlorobenzylalcohol and Compound A with3,5-dimethyltetrahydro-1,3,5-(2H)-thiadiazine-2-thione are demonstratedin Table 15 and Table 16, respectively. Table 15 is an example of noeffect by the combination of two compounds. The activity of Compound A(MIC=0.31 ppm) was not affected by the absence or presence up to 500 ppmof 2,4-dichlorobenzylalcohol. The activity of 2,4-dichlorobenzylalcohol(MIC=500 ppm) was not affected by Compound A from 0 to 5 ppm. Thus, noincrease or decrease of activity can be attributed by the combination.Table 16 is an example of antagonistic effect by the combination ofCompound A and 3,5-dimethyltetrahydro-1,3,5-(2H)-thiadiazine-2-thionebecause there was a loss of activity of Compound A due to the presenceof 3,5-dimethyltetrahydro-1,3,5-(2H)-thiadiazine-2-thione in thecombination.

It is apparent that many modifications and improvements may be madewithout departure from the scope of the invention which is not to belimited as recited in the appended claims.

What is claimed:
 1. A microbicidal composition comprising a synergisticmixture the first component of which is a 3:1 ratio of5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-oneand the second component of which is selected from the group consistingof p-tolyldiiodomethylsulfone; 3-iodo-2-propynylbutylcarbamate; and1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride where theratio of first component to second component is in the range of fromabout 8:1 to about 1:200.
 2. The composition of claim 1, wherein theratio of the first component to the second component,p-tolyldiiodomethylsulfone, is in the range of from about 8:1 to about1:20.
 3. The composition of claim 1, wherein the ratio of the firstcomponent to the second component, 3-iodo-2-propynyl butylcarbamate, isin the range of from about 1:1 to about 1:25.
 4. The composition ofclaim 1, wherein the ratio of the first component to the secondcomponent, 1-(3-choloroallyl)-3,5,7-triaza-azoniaadamantane chloride, isin the range of from about 1:6.2 to about 1:200.
 5. A composition forinhibiting the growth of microorganisms selected from the groupconsisting of bacteria, fungi and mixtures thereof in a locus subject tocontamination by said microorganisms comprising about 10 to about 50 ppmof the composition of claim
 1. 6. A method for inhibiting the growth ofa member selected from the group consisting of bacteria, fungi, algaeand mixtures thereof in a locus subject to contamination by said member,which comprises incorporating onto or into the locus, in an amount whichis effective to adversely affect the growth of said member, thecomposition of claim
 1. 7. The method of claim 6 wherein the locus in anaqueous medium.
 8. The method of claim 7 wherein the composition isbetween from about 5 to about 100 ppm.